This application responds to laboratory, analytical, and collaborative components mentioned in the RFA. Specifically, we propose to integrate epidemiological risk factor information with a decision analytical approach, using existing data sets and stored biological specimens, and establishing a multidisciplinary collaboration between the FHS, Boston University Medical Center, Boston University Mathematics Department and the Tufts University Human Nutrition Research Center on Aging. Aim 1. To test the utility of homocysteine (tHcy) (to be measured), C-reactive protein (CRP) (to be measured), lipoprotein (a) [Lp(a] (already determined) as predictors of coronary heart disease (CHD) over and above traditional risk factor measures. Levels of these markers will be determined with a nested case cohort design, utilizing a baseline examination that includes already obtained information on conventional risk factors for the Framingham Offspring and 12 years of follow up for cardiovascular disease events. New measurements of hsCRP will be made in the Framingham laboratory and homocysteine will be done at Tufts University by Dr. Jacob Selhub. Aim 2. To test the ability of new factors (tHcy, CRP and Lp[a]) at different levels of coronary risk as assessed by using the traditional risk factors alone, considering 0-6%, 6-20% and >20% initial risk of a coronary event. The utility of newer risk measures to predict an increase in the absolute risk of coronary events at pre-specified absolute levels of risk will be estimated. Aim 3. To develop new CHD risk prediction equations that will incorporate CRP and homocysteine measurements to assess the risk of coronary heart disease. This aim will include estimates of CHD risk over 12 years for the second generation Offspring and will incorporate data from the older first generation cohort where homocysteine and CRP have already been measured and 12 years of follow up for coronary disease events is also available.